The objective was to test calibration of an eye oximeter (EOX) in a vitiligo swine eye and correlate retinal venous oxygen saturation (SrvO2), mixed venous oxygen saturation (SvO2), and cardiac output (CO) during robust changes in blood volume. Ten anesthetized adult Sinclair swine with retinal vitiligo were placed on stepwise decreasing amounts of oxygen. At each oxygen level, femoral artery oxygen saturation (SaO2) and retinal artery oxygen saturation (SraO2) were obtained. After equilibration on 100% O2, subjects were bled at 1.4 ml · kg−1· min−1for 20 min. Subsequently, anticoagulated shed blood was reinfused at the same rate. During graded hypoxia, exsanguination, and reinfusion, SraO2and SrvO2were measured by using the EOX, and CO and SvO2were measured by using a pulmonary artery catheter. During graded hypoxia, SraO2correlated with SaO2( r = 0.92). SrvO2correlated with SvO2( r = 0.89) during exsanguination and reinfusion. SvO2and SrvO2correlated with CO during blood removal and resuscitation ( r = 0.92). Use of vitiligo retinas improved the calibration of EOX measurements. In this robust hemorrhage model, SrvO2correlates with CO and SvO2across the range of exsanguination and resuscitation.